Faculty Bibliography

Importance/UNASSIGNED:Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD. Objective/UNASSIGNED:To determine whether metformin use is associated with reduced odds of developing AMD. Design, Setting, and Participants/UNASSIGNED:This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020. Exposures/UNASSIGNED:Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims. Main Outcomes and Measures/UNASSIGNED:Risk of developing AMD. Results/UNASSIGNED:A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]). Conclusion and Relevance/UNASSIGNED:In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.

Fuchs endothelial corneal dystrophy (FECD) is the most common posterior corneal dystrophy and the leading indication for corneal transplantation in the United States. FECD is slowly progressive, and patients develop gradual corneal endothelial decompensation, eventually resulting in failure of the endothelium to maintain corneal deturgescence. Medical management consists of topical hyperosmotic agents to facilitate dehydration of the cornea, but surgical intervention is often required to regain corneal clarity. The surgical management of FECD has evolved over the past two decades as corneal transplantation techniques have allowed for more selective keratoplasty and replacement of only the diseased layers of the cornea. Prior surgical management consisted of penetrating keratoplasty (PK) that carried significant intraoperative risks associated with "open sky" as well as postoperative risks of graft rejection, wound dehiscence, postoperative astigmatism, and prolonged visual rehabilitation. In the past 15 years, endothelial keratoplasty (EK) has become the treatment of choice for endothelial disease, significantly reducing the risks associated with the surgical treatment of FECD. Here we discuss the current surgical management of FECD, including the introduction of Descemet stripping only (DSO), and highlight future investigative efforts.

INTRODUCTION/BACKGROUND:Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. METHODS:Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. RESULTS:In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. CONCLUSION/CONCLUSIONS:Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier, NCT03525678.

PURPOSE/OBJECTIVE:To quantitatively analyze the angle anatomy in eyes with a Boston type 1 keratoprosthesis (KPro) using anterior segment optical coherence tomography (AS-OCT) and to assess the diagnostic ability of AS-OCT in KPro-associated glaucoma. METHODS:AS-OCT (RTVue) images from KPro eyes with and without glaucoma were reviewed. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular-iris angle at 500 μm from the scleral spur (TIA500), and trabecular-iris surface area at 500 μm from the scleral spur (TISA500) were measured by 2 observers masked to the diagnosis. The measurements for each visible quadrant were compared between KPro eyes with and without glaucoma. RESULTS:Twenty-two eyes with glaucoma and 17 eyes without glaucoma from 39 patients with KPro were included. Of the 4 quadrants imaged, the temporal angle was the most visible (79.5%) and angle measurements of the temporal quadrant were the only ones that differentiated the 2 groups: the mean AOD500, TIA500, and TISA500 were significantly lower in KPro eyes with glaucoma than without glaucoma (388.2 ± 234.4 μm vs. 624.5 ± 310.5 μm, P = 0.02; 26.1 ± 14.0 degrees vs. 39.1 ± 17.1 degrees, P = 0.03; and 0.15 ± 0.09 mm vs. 0.23 ± 0.12 mm, P = 0.03; respectively). The highest area under the receiver operating characteristic curve for detecting glaucoma was 0.75 for temporal TIA500 (95% confidence interval 0.57-0.94, P = 0.02) with 50% specificity at 80% of sensitivity and a cutoff value of 37 degrees. CONCLUSIONS:The temporal angle was the most visible on AS-OCT in eyes with a KPro. Significant narrowing of the temporal angle detected on AS-OCT was associated with glaucoma in these eyes.

Among the group of diseases comprising corneal dystrophies, there are a number for which contact lenses may be considered. For example, soft contact lenses may be beneficial in the management of recurrent corneal erosions and advanced bullous keratopathy and may lead to disease attenuation in some conditions. They also may be used in conjunction with surgical procedures to promote tissue healing and patient comfort in the postoperative period. Rigid contact lenses may be beneficial in the setting of irregular astigmatism. The present review of the literature will discuss the use of contact lenses in the management of corneal dystrophies.

PURPOSE:To assess outcomes and glaucoma management in eyes with aniridia following Boston type 1 Keratoprosthesis (KPro) implantation. DESIGN:Retrospective, interventional comparative case series. METHODS:The population included patients with aniridia and patients with other preoperative diagnoses (excluding Stevens-Johnson syndrome, mucous membrane pemphigoid, and congenital disorders) who underwent KPro implantation at Massachusetts Eye and Ear with at least 2 years of follow-up. One eye per patient was selected based on the longer follow-up time. The main outcome was intermediate and long-term outcomes related to glaucoma. RESULTS:The aniridia (n = 22) and comparison (n = 61) groups had similar preoperative visual acuity (VA, mean ± standard deviation, 1.86 ± 0.52 logMAR, P = .33) and follow-up time (65.6 ± 26.3 months, P = .25). Before KPro implantation, eyes with aniridia had more glaucoma (76.2%) and glaucoma surgery (57.1%) than comparison eyes (51.8%, P = .053; 23.2%, P = .005, respectively). More Ahmed valves were co-implanted with KPro in aniridia (47.6%) vs comparison eyes (17.9%, P = .008). At final follow-up, more aniridia eyes had glaucoma (90.5%) than comparison eyes (64.3%, P = .02), but the 2 groups had similar percentages of eyes with cup-to-disc ratio (CDR) >0.8 (23.8% vs. 30.4%, P = .57) or CDR progression of ≥0.2 (42.9% vs 44.6%, P = .89, respectively). None of the eyes with prophylactic tube implantation developed glaucoma. Eyes with and without aniridia did not differ in post-KPro VA improvement (72.7%, 72.1%, P = .96), and final VA (1.28 ± 0.79 logMAR, 1.23 ± 0.98 logMAR, P = .51). CONCLUSION:Despite a higher glaucoma prevalence, eyes with aniridia achieved similar VA as comparison eyes with more than 5 years of mean follow-up time. Boston KPro offers satisfactory visual rehabilitation in aniridia when glaucoma is managed aggressively.